Fig. 1: Hallmarks of a genomically distinct subclass of head and neck cancer.

Characterization of the copy number alteration (CNA)-quiet subclass. CNA-quiet oral cancers are predominantly wild-type TP53, frequently harbor CASP8 and HRAS mutations, exhibit a cohesive growth pattern, are often well-differentiated, and have a less immunosuppressed tumor immune microenvironment. Both oral cancer subclasses are most commonly located on the tongue. CNA-quiet tumors are also frequently found in the vestibule of mouth and cheek mucosa, while CNA-other cancers are more commonly located on the floor of mouth. The CNA-quiet group is enriched for females without tobacco use, less or no alcohol use, and a higher age at diagnosis. Patients with CNA-quiet oral cancers demonstrate a more favorable 5-year overall survival compared to CNA-other oral cancers. Figure 1 is created with BioRender.com released under a Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International license.